U.S. patent number 3,669,979 [Application Number 04/690,376] was granted by the patent office on 1972-06-13 for novel process for the production of 2-benzothiazolyl-phenol and derivatives thereof employing phosphorus trichloride as a catalyst.
This patent grant is currently assigned to GAF Corporation. Invention is credited to Harlan B. Freyermuth.
United States Patent |
3,669,979 |
Freyermuth |
June 13, 1972 |
NOVEL PROCESS FOR THE PRODUCTION OF 2-BENZOTHIAZOLYL-PHENOL AND
DERIVATIVES THEREOF EMPLOYING PHOSPHORUS TRICHLORIDE AS A
CATALYST
Abstract
A method of preparing heterocyclic derivatives selected from the
formulae: ##SPC1## Wherein X is selected from hydrogen, lower
alkyl, lower alkoxy, and halogen; Y is selected from hydroxy and X;
Z is selected from nitrogen, oxygen, and sulfur by reacting an o-
aminobenzenethiol, o-aminophenol, or o- aminoaniline and
substituted derivatives thereof with an ortho-substituted benzoic
acid or 2-substituted naphtholic acid in the presence of a catalyst
comprising phosphorus trichloride. The compounds produced by the
process of the present invention are useful as stabilizers in
various organic media, e.g., organic plastics, oils, etc. and as
intermediates in the production of dyestuffs and fluorescent
compounds.
Inventors: |
Freyermuth; Harlan B. (Easton,
PA) |
Assignee: |
GAF Corporation (New York,
NY)
|
Family
ID: |
24772214 |
Appl.
No.: |
04/690,376 |
Filed: |
December 14, 1967 |
Current U.S.
Class: |
548/179; 548/178;
548/310.7; 562/490; 548/152; 548/224; 562/473; 562/493 |
Current CPC
Class: |
C07D
235/18 (20130101); C07D 277/66 (20130101); C07D
263/57 (20130101) |
Current International
Class: |
C07D
235/00 (20060101); C07D 235/18 (20060101); C07D
263/00 (20060101); C07D 263/57 (20060101); C07D
277/00 (20060101); C07D 277/66 (20060101); C07d
091/44 (); C07d 085/48 (); C07d 049/38 () |
Field of
Search: |
;260/304,307.4,309.2 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Grimmel et al., Chem. Abstracts, 40:3457 (1946).
|
Primary Examiner: Mazel; Alex
Assistant Examiner: Gallagher; R. J.
Claims
I claim:
1. A process for producing heterocyclic derivatives of the
formulas: ##SPC7##
wherein
X is selected from H, lower alkyl, lower alkoxy, and halogen;
Y is selected from OH and X, wherein X is as defined above; and
Z is selected from NH, O, and S, which comprises condensing a
compound I selected from the formulas:
with a compound II selected from the formulas:
wherein X and Y are defined above, in the presence of a catalyst
comprising phosphorus trichloride in an amount of from about 0.5 to
about 2.0 mols per mol of compound I and a solvent selected from
organic aromatic hydrocarbons, aniline and mono- and di-lower alkyl
substituted aniline, said process being conducted in two stages,
the first stage being conducted at a temperature of from about
40.degree. to about 80.degree. C to affect the reaction of said
compound I with said phosphorus trichloride to form a phosphazo
intermediate with the second stage being conducted at a temperature
of from about 90.degree. to about 120.degree. C to affect the
reaction of said phosphazo intermediate with said Compound II.
2. The process of claim 1 wherein said Compound I is
o-aminobenzenethiol, and said Compound II is salicyclic acid, the
desired heterocyclic derivative being 2-benzothiazolylphenol.
3. The process of claim 1 wherein said solvent is toluene.
4. The process of claim 1 wherein said solvent is
dimethylaniline.
5. The process of claim 2 wherein said solvent is toluene.
6. The process of claim 2 wherein said solvent is dimethylaniline.
Description
The present invention is directed to a novel process for the
preparation of certain heterocyclic derivatives, and more
particularly, to an improved process of producing certain
heterocyclic derivatives in high yield by the use of a phosphazo
reaction employing as the catalyst phosphorus trichloride
The heterocyclic derivatives that are produced in accordance with
the novel process of the present invention have been known in the
prior art and have been prepared by various methods. Thus, in the
Journal of Organic Chemistry, Volume 18, Pages 422-425(1953), it is
reported by Robert G. Charles and Henry Freiser that
2-benzothiazolyphenol can be produced by condensing salicylic acid
and o-aminobenzenethiol. The structure of the compound having a
melting point of 132.degree.- 133.degree. C was proved by studying
the ultraviolet absorption spectra of the product that was
prepared.
While such a procedure outlined by Charles and Freiser is effective
to produce the desired 2-benzothiazolyphenol, the procedure set
forth and described in the literature produced a product of poor
yield after distillation of black-colored reaction mixture. Thus,
it is reported that yields of only about 47 percent were produced
by this prior art method. Similar procedures for the production of
analogous compounds have also proven to be unsatisfactory, both
from the standpoint of yield of product and purity of the product
that is produced.
Accordingly, it has long been the desire of the industry to provide
a new process for the production of certain heterocyclic
derivatives which process could be effective to produce such
derivatives in high yield and in high purity. Particularly, it has
been the desire of the industry to provide a new process for the
production of the valuable product 2-benzothiazolyphenol, which new
process would eliminate the inherent deficiencies of the prior art
process described in the literature.
In accordance with the present invention, however, it has now been
discovered that by employing the particular process of the present
invention, wherein a phosphazo reaction is conducted by the
employment of phosphorus trichloride as a catalyst, it is possible
to produce certain heterocyclic derivatives in yields of
approximately 90 percent. Additionally, it has been discovered in
accordance with the present invention that it is possible to
produce 2-benzothiazolylphenol in yields of substantially 90
percent by the reaction of o-aminobenzenethiol and salicylic acid
in a phosphazo reaction employing phosphorus trichloride as a
catalyst.
Accordingly, it is a principal object of the present invention to
provide a novel process for the production of certain heterocyclic
derivatives, which process eliminates the inherent deficiencies of
prior known processes.
It is a further object of the present invention to provide such a
novel process for the production of certain heterocyclic
derivatives wherein a phosphazo reaction is conducted employing
phosphorus trichloride as the catalyst.
A still further object of the present invention is to provide a
novel process for the production of certain heterocyclic
derivatives wherein yields of approximately 90 percent can be
obtained by employing a catalyst comprising phosphorus
trichloride.
A still further object of the present invention is to provide a
novel process for the production of 2-benzothiazolylphenol by the
reaction of o-aminobenzenethiol and salicylic acid in a phosphazo
reaction employing a catalyst comprising phosphorus
trichloride.
Still further objects and advantages of the novel process of the
present invention will become more apparent from the following more
detailed description thereof.
The present invention relates to the production of certain
heterocyclic derivatives of the following structural formulas.
##SPC2##
wherein X is selected from hydrogen, lower alkyl, e.g., methyl,
ethyl, n-propyl, isopropyl, n-butyl, t-butyl, n-amyl, iso-amyl,
etc., lower alkoxy, e.g., methoxy, ethoxy, n-propoxy, isopropoxy,
n-butoxy, t-butoxy, etc., and halogen, e.g., chlorine, bromine,
iodine, etc.; Y is selected from hydroxy and X; and Z is selected
from nitrogen, oxygen, and sulfur.
Such compounds are prepared by condensing an o-aminobenzenethiol,
o-aminophenol, o-aminoaniline, or substituted derivatives thereof
with an o-substituted benzoic acid or 2-substituted naphtholic
acid. The process of the present invention is particularly suitable
for the production of 2-benzothiazolylphenol by the condensation of
o-aminobenzenethiol and salicylic acid.
Exemplary o-aminobenzenethiols, o-aminophenols, and o-aminoanilines
suitably employed in the condensation reaction of the present
invention are: ##SPC3##
Similarly, exemplary benzoic and naphtholic acid derivatives
suitably employed in the phosphazo condensation process of the
present invention include: ##SPC4##
Since the process of the present invention is particularly suitable
for the preparation of 2-benzothiazolylphenol by the condensation
of o-aminobenzenethiol and salicylic acid, the process of the
present invention will now be further described primarily with
reference to the production of this product.
As noted above, the process of the present invention comprises a
phosphazo reaction wherein the 2-aminobenzenethiol or analogous
material is condensed with salicylic acid or analogous material in
the presence of phosphorus trichloride. While not wishing to be
bound by any particular theory, it is hypothesized that the
aromatic amine first reacts with the phosphorus trichloride to form
a phosphazo intermediate which intermediate subsequently reacts
with the aromatic carboxylic acid to produce the anilide. In the
case of 2-aminobenzenethiol and salicylic acid to produce
2-benzothiazolylphenyl, it is hypothesized that spontaneous
cyclization occurs in the acidic media after or simultaneous with
the anilide formation.
The phosphazo reaction with the present invention is generally
carried out in the presence of an organic solvent. Generally, the
solvent that is employed is one selected from organic aromatic
hydrocarbons and organic aromatic amines. Exemplary organic
aromatic hydrocarbons include, for example, benzene, toluene,
ortho-, meta-, and para-xylene, etc. Similarly, exemplary aromatic
amine solvents which can be employed in the phosphazo reaction of
the present invention include, for example, aniline, mono-lower
alkyl substituted derivatives of aniline, and di-lower alkyl
substituted derivatives, e.g., dimethylaniline.
The organic aromatic hydrocarbon solvents, particularly toluene,
are the preferred solvents in accordance with the process of the
present invention. Thus, it has been found that the employment of
such aromatic hydrocarbon solvents produces a slightly higher yield
of desired heterocylic derivative than is obtained by the
employment of the organic aromatic amine.
The amount of solvent employed in the reaction system in accordance
with the present invention is not in any way critical. Accordingly,
great excesses of solvent in the system in no way interfere with
the reaction taking place and in no way adversely affect the yield
or purity of the product. The solvent that is employed in the
system is merely removed from the reaction system after completion
of the reaction by conventional solvent removal systems.
The process of the present invention is generally carried out in
two stages or steps. The first step in the reaction of
2-aminobenzenethiol or an analogous material and phosphorus
trichloride is exothermic and is generally carried out at a
temperature of from about 40.degree. to 80.degree. C, preferably
about 60.degree. C with external cooling. In this step, the
phosphazo intermediate is prepared by the reaction of phosphorus
trichloride with the 2-aminobenzenethiol or analogous material. The
second step of stage between such phosphazo intermediate and the
salicylic acid or analogous material is generally carried out at an
elevated temperature of from about 90.degree. to 120.degree. C,
preferably from about 105.degree. to 110.degree. C. This
temperature is very near the boiling point of toluene and thus,
reflux conditions can be utilized.
It has been found that by carrying out both steps at an elevated
temperature an inferior product in low yield is produced. The
process of the present invention can be carried out either by
employing a single reaction vessel initially kept at approximately
40.degree. to 80.degree. C with subsequent raising of the
temperature of reaction to the higher temperature of 90.degree. to
120.degree. C or can be conducted in two separate reaction vessels,
wherein the product of the first reaction conducted at the lower
temperature is completely removed and passed into the second vessel
at a higher temperature in order to conduct the second step or
stage of the reaction.
While the two reactants in the novel process of the present
invention react in substantially stoichiometric amounts it has not
been found disadvantageous to employ an excess of either the
reactants. Thus, the employment of a stoichiometric excess of
either of the reactants does not adversely affect the purity or
yield of the reaction product, it only being necessary to remove
excess reactant after the completion of the reaction. This again
can be accomplished in any conventional manner. For purposes of
economics, however, it is preferred to employ substantially
stoichiometric amounts of the reactants.
As noted above, the phosphazo reaction of the present invention is
accomplished in the presence of a catalyst comprising phosphorus
trichloride. The amount of phosphorus trichloride catalyst that is
employed in the reaction process of the present invention generally
varies from about 0.5 to 2 moles of phosphorus trichloride per mole
of 2-aminobenzenethiol or analogous reactant. Preferably, the
phosphorus trichloride catalyst and 2-aminobenzenethiol or
analogous reactant are employed in substantially equi-molar
amounts. It is, of course, obvious that lesser or greater amounts
of the catalyst material can be employed where desired for specific
purposes.
The following compounds are representative of those which are
produced by the novel phosphazo reaction of the present invention:
##SPC5##
The following specific examples illustrate various embodiments of
the present invention. It is to be understood, however, that such
examples are presented for purposes of illustration only, and the
novel process of the present invention is in no way to be deemed as
limited thereby.
EXAMPLE 1
A 50 liter flask having a multi-neck entrance attachment was
equipped with an air driven stirrer, thermometer, condenser,
hydrogen chloride, scrubber, "cold finger" (made from a 28 mm.
diameter and 32 inch long glass tube which had been sealed at one
end), a 1 liter dropping funnel and an electric heating mantle. To
this flask was charged 18.75 liters toluene, 2,070 g. (15 moles)
salicylic acid and 1,875 g. (15 moles) aminobenzenethiol. The "cold
finger" was filled with acetone to the liquid level of the flask.
During an hour and twenty minutes. 1,695 g. of phosphorus
trichloride was added by means of the dropping funnel. Small pieces
of dry ice were continually added to the cold finger to absorb some
of the heat from the exothermic reaction. The temperature was
allowed to slowly climb to 43.degree. C during the addition period.
The creamy white slurry of the phosphazo addition was slowly heated
by the electrical heating mantle. At 90.degree. - 95.degree. C,
hydrogen chloride began to evolve rapidly and some slight flooding
of the condenser occurred. The slight flooding subsided at
107.degree. C and the temperature was raised to the reflux
(111.degree. C) for 4 hours after which time, the evolution of
hydrogen chloride has subsided. The reaction was allowed to cool
over night and the following morning, 8 liters of 20 percent
weight/volume sodium carbonate were gradually added through a
dropping funnel to neutralize all the acid and make the reaction
mixture slightly alkaline (pH 8.9). The toluene was steam distilled
from the reaction mixture (16 liters was collected). Upon cooling,
the tan or light colored product was filtered on a large ceramic
filter The wet cake (5,170 g.) was placed in glass trays and dried
over night in vacuum ovens at 60.degree. C. The dried product
(3,190 g.) melted at 129.degree.- 133.degree. C and the yield was
over 90 percent of theoretical. The product corresponded to the
formula:
EXAMPLE 2
A 1 liter three-neck flask equipped with a stirrer, thermometer, a
Thermo-Watch temperature controller and an electric heating mantle
was charged with 55.2 g. (0.4 mole) salicylic acid, 121 g. (130
ml.) dimethylaniline (1.0 mole), and 50.0 g. (43 ml.; 0.4 mole)
2-aminobenzenthiol. The mixture was warmed to 60.degree. C with
continual agitation and 45.2 g. (29.2 ml.; 0.33 mole) phosphorus
trichloride was added dropwise by means of a separatory funnel
during 40 minutes. The temperature was maintained at 60.degree. C
for seven hours, whereupon the mixture was cooled to room
temperature and 400 ml. water and 30 ml. concentrated hydrochloric
acid were added. The mixture was stirred over night and the
precipitated product was filtered on a Buchner funnel. The wet cake
was dried in a vacuum oven. The 2-benzothiazolylphenol weighed 81,3
g. and melted at 130.degree.- 132.degree. C. The yield was 89
percent of theory.
EXAMPLE 3
In the manner described in Example 1, approximately stoichiometric
amounts of the following reactants were condensed to produce the
corresponding heterocyclic derivative using phosphorus trichloride
as the catalyst. In all cases, a yield of approximately 90 percent
of the desired product was obtained. ##SPC6##
The compounds produced in accordance with the process of the
present invention are useful as stabilizers in various organic
media, e.g., organic plastics, oils, etc., and as intermediates in
the production of dyestuffs and fluorescent compounds. Thus,
reference is made to my co-pending application in which
2-benzothiazolylphenol is employed as a starting material in the
production of a highly fluorescent dyestuff.
While various embodiments of the present invention have been
described with reference to the specific examples it is to be
understood that the present invention is in no way to be deemed as
limited thereto, but should be construed as broadly as all or any
equivalents thereof.
* * * * *